Clinical implication of expression of cyclooxygenase-2 and peroxisome proliferator activated-receptor γ in epithelial ovarian tumours

Abstract

Expression of cyclooxygenase (COX)-2 plays a key role in tumorigenesis and development and peroxisome proliferator-activated receptor γ (PPARγ) has been implicated in the control of COX-2 expression in some tissues. The aim of this study is to investigate (1) whether expression of COX-2 and PPARγ is associated with ovarian carcinogenesis and progression of ovarian tumours and (2) whether COX-2 expression is controlled through ligand-mediated activation of PPARγ in ovarian carcinoma cells. For this purpose, the presence of COX-2 and PPARγ was immunohistochemically examined in 71 epithelial ovarian carcinomas, 18 borderline tumours and 23 benign tumours and the levels of COX-2 and PPARγ proteins were determined by enzyme immunoassay in four benign tumours, three borderline tumours and 12 carcinomas. The frequency of COX-2 and PPARγ detection was significantly increased and decreased as lesions progressed to carcinoma, respectively. The COX-2 protein was not detected in the three borderline tumours, whereas PPARγ protein was detected in all of them. COX-2 protein was detected in eight of the 12 carcinomas, whereas PPARγ protein was detected in only two cases. In addition, PPARγ protein was not detected in all of the eight carcinomas in which COX-2 protein was detected, suggesting that expression of PPARγ and COX-2 was in a reciprocal relationship. Furthermore, in cultured ovarian carcinoma cells, Western blot revealed that PPARγ and COX-2 expression was regulated conversely as a result of stimulation by 15-deoxy-Δ 12, 14 PGJ2 (15-PGJ2), a PPARγ activator. In addition, 15d-PGJ2 suppressed tumour necrosis factor-α-induced-COX-2 expression, confirming the reciprocal correlation between COX-2 and PPARγ. From these results, it was suggested that PPARγ activation might suppress COX-2 expression via the nuclear factor-κB pathway in the ovarian carcinoma cells and that low expression of PPARγ and high expression of COX-2 might be involved in carcinogenesis and progression of ovarian tumours. © 2004 Cancer Research UK.